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Oxime reactivators play an integral role in the treatment of acute OP exposure by returning function to OP-inhibited AChE. Our laboratory has synthesized and patented a platform of oxime reactivators (US Patent 9,227,937) that have provided central neuroprotection through returning function to OP-inhibited AChE in the brain and preservation of neuronal and glial structures from damage in a rat model; the current US-approved oxime, pralidoxime, does not provide central neuroprotection. Thus, returning function to other OP-inhibited serine hydrolases by these novel oximes could provide additional secondary neuroprotection. Rat brain proteins were studied using activity-based protein profiling (ABPP) for serine hydrolase targets of a highly relevant sarin surrogate, nitrophenyl isopropyl methylphosphonate (NIMP), alone or in combination with Oxime 20, our lead novel AChE reactivator. ABPP indicated that NIMP significantly inhibited 6 serine hydrolases, and of these were the well-known serine hydrolases fatty acid amide hydrolase and monoacylglycerol lipase, which are important in endocannabinoid signaling. Oxime 20 administration after NIMP treatment showed only limited remediation of the inhibition experienced by these targets. The impact of this study is the identification of secondary serine esterase targets that could be explored for esterase reactivating therapeutics for the treatment of OP poisoning.<\/jats:p>","DOI":"10.1093\/toxsci\/kfag024","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T12:44:57Z","timestamp":1772714697000},"source":"Crossref","is-referenced-by-count":0,"title":["Serine hydrolase targets of a sarin surrogate anticholinesterase and oxime-mediated reactivation in rat brain"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8677-539X","authenticated-orcid":false,"given":"Chiquita Y","family":"Price","sequence":"first","affiliation":[{"name":"Comparative Biomedical Sciences Department, College of Veterinary Medicine, Center for Environmental Health Sciences, Mississippi State University , Mississippi State, MS 39762,","place":["United 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